Alleviation of acute and chronic graft-versus-host disease in a murine model is associated with glucocerebroside-enhanced natural killer T lymphocyte plasticity

BACKGROUND: Natural killer T (NKT) lymphocytes play a role in graft-versus-host disease GVHD (GVHD). Glucocerebroside (GC) is a naturally occurring glycolipid that plays a role in the immune modulation of NKT lymphocytes. This study aims to determine the effect of GC in murine models of semiallogeneic/acute and chronic GVHD. METHODS: Acute and chronic GVHD were generated by fusion of splenocytes from C57BL/6 to (C57BL/6xBalb/c) F1 mice, and from B10.D2 donor mice into Balb/c, respectively. Recipients were treated daily with GC. Histological and immunological parameters of GVHD were assessed. RESULTS: Treatment with GC significantly alleviated GVHD in both models The beneficial effect of GC was associated with an increase in the intrahepatic/peripheral NKT lymphocyte ratio in the semiallogeneic/acute model. This ratio was decreased in the chronic GVHD model. A significant increase in intrahepatic CD8+ lymphocyte trapping was noted in the semiallogeneic/acute model, whereas the opposite effect was observed in the chronic GVHD model. Administration of GC led to decreased serum interferon-gamma and increased serum interleukin-4 levels in the Th1-mediated model, whereas the opposite effect was observed in the Th2-mediated models. CONCLUSIONS: GC ameliorates GVHD in both Th1- and Th2-mediated murine models, suggesting it is able to differentially affect the immune system. GC may alleviate immunologically incongruous disorders, and may be associated with "fine tuning" of immune responses.